Abstract
Inhibiting cystathionine gamma-lyase (CSE) to prevent H 2 S synthesis augments constriction in isolated mesenteric and renal arteries, but H 2 S regulation of resistance in these vascular beds in vivo is unknown. This study evaluated regulation of blood flow and resistance in the mesenteric and renal vascular beds in chronically instrumented rats. Based on studies in isolated arteries, we hypothesized that endogenous production of H 2 S by CSE decreases vascular resistance more in mesenteric than in renal arteries. Rats were anesthetized with inhaled isofluorane (2%) and instrumented with femoral vein catheters, a telemeter blood pressure device and a pulsed Doppler flow probe (Crystal Biotech) on either the superior mesenteric artery or the renal artery (after denervation of the renal artery by removing all visible nerves and painting the surface of the artery with 10% phenol). After five to seven days of recovery from surgery, arterial pressure (AP), heart rate (HR) and relative blood flow (Q) was recorded. Rats then received a daily injection of the irreversible CSE inhibitor, propargylglycine (PAG, 50 mg/kg/day). After five injections, AP was significantly increased in rats with mesenteric flow probes (110±3 start to 122±4 mmHg post PAG, p<0.05 n=7 rats per group). Relative mesenteric resistance (AP/Q) normalized to starting values was increased in PAG rats (150±7% starting value) compared to no change in rats receiving saline (98±3% starting value) (p<0.05, n=7 rats per group). In the rats instrumented with renal flow probes, AP was also increased in the PAG but not in the saline rats (115±6 start to 143±5 mmHg post PAG, p = 0.0014) and calculated renal resistance increased (198% ± 14% versus 103 ± 5% starting value, p=0.0003, n = 5 rats). Heart rate was not changed by any of the treatments. Our results suggest that endogenous H 2 S is an important regulator of vascular resistance in both the mesenteric and renal circulations and that the contribution may be larger in the renal bed than in the mesenteric bed.
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